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Hepatitis C virus entry: possible targets for therapy
  1. J M Timpe,
  2. J A McKeating
  1. Institute for Biomedical Research, University of Birmingham, Birmingham, UK
  1. Professor J A McKeating, Institute for Biomedical Research, The Medical School, Vincent Drive, Birmingham B15 2TT, UK; j.a.mckeating{at}bham.ac.uk

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Hepatitis C virus (HCV), a major cause of liver disease, has been a challenging opponent for researchers and clinicians for more than 35 years. The introduction of diagnostic tests in the mid-1970s revealed that the causative agent of most cases of post-transfusion hepatitis was neither hepatitis A virus (HAV) nor B (HBV). Bearing the moniker non-A non-B hepatitis (NANB), the virus eluded identification for nearly 15 years. Attempts to isolate the virus by standard immunological techniques were unsuccessful, so, in 1989, Choo and colleagues used viral antigen to screen for reactivity with patient-derived antibodies.1 Expression of a cDNA library of genetic material cloned from the plasma of an infected chimpanzee identified clones that were reactive with NANB-positive patient sera. The genome was identified as a single-stranded RNA of approximately 10 000 nucleotides and the virus named hepatitis C. At the time of its discovery HCV imposed a significant healthcare burden, and it continues to do so today.

EPIDEMIOLOGY

The World Health Organization estimated that at least 170 million people are currently infected with HCV, with an additional 3–4 million new infections occurring each year.2 In the developed world, intravenous drug use is the greatest risk factor, where an epidemiological survey in 2000 reported that 80% of intravenous drug users in Europe were infected with HCV.3 Due to effective screening programmes, which reduced the incidence of post-transfusion hepatitis C infection from 3.84% to 0.57% per person in the USA, treatment with blood or blood products is no longer a significant risk factor in the developed world.46 However, developing countries lack the resources for such measures, and the incidence of transfusion-acquired HCV remains high. Unsafe therapeutic injections and unlicensed medical practitioners are additional risk factors for acquiring HCV infection in many developing countries.6 7 For example, insufficient …

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